Diseases of the Pituitary Gland

Diseases of the pituitary gland are common, and the most frequently encountered lesions within the sella turcica and pituitary are described and illustrated in details in this chapter. The lesions present within this chapter include cysts and malformations, vascular lesions, inflammatory disorders, infectious diseases, systemic diseases, and both benign and malignant neoplasms. The most common neoplasms of the pituitary are the pituitary adenomas, and these are described in detail including the numerous subtypes depending on the cell differentiation and hormone production. The chapter contains numerous tables and figures illustrating the pathological findings.

Congenital Malformations and Perinatal Diseases

This chapter describes and illustrates the changes of the central nervous system in congenital malformations and perinatal diseases; it also provides insights in the genetic abnormalities associated with these conditions. Congenital malformations include neurulation failure resulting in neural tube closure defects; disorders of development of the prosencephalon; malformations of the cortical plate (neuronal heterotopia, polymicrogyria, lissencephaly, and focal cortical dysplasia [a frequent cause of epilepsy in children]); and disorders of hindbrain development, particularly malformations of the cerebellum. Destructive lesions of developing brain are described in association with a variety of situations generally resulting in “hypoxia-ischemia.” They may affect the neocortex, causing porencephaly or hydranencephaly; the basal ganglia (status marmoratus); or the white matter (perinatal telencephalic leukoencephalopathy and periventricular leukomalacia).

Hereditary Metabolic Diseases

This chapter describes and illustrates the morphological central nervous system changes in hereditary metabolic disorders. In some disorders, the metabolic derangements are most prominent in the cytosol and are linked to the dysfunction of a single cellular organelle. In these disorders, there may be intracellular accumulation of an intermediate metabolite, resulting in “storage” or accumulation of the abnormal substance within the cell. The organelles most commonly involved in these disorders are lysosomes, peroxisomes, mitochondria, and the cytoplasmic compartment. Other disorders are defined by an enzyme deficiency; by the biochemical pathways involved (metabolic disorders of sugars, copper, amino acids, or structural protein); or only by morphologic/clinical features.

Vascular Pathology

The classification of vascular diseases of the central nervous system proposed here considers at first two large groups of entities: large intraparenchymal hemorrhage due to rupture of blood vessels and then, infarction from occlusion of major vessels. The underlying vessel abnormality is discussed, as are the reactions over time of nervous tissue to irreversible injury. Intracranial hemorrhages can also be seen in the context of rupture of vessels, with outpouring of blood into the subarachnoid spaces in cases of ruptured aneurysm or of vascular malformation. Small vessel disease is considered separately, these are instances of lesions affecting the microcirculation; clinical manifestations include dementia, encephalopathies, or multifocal neurologic deficits, the result of multiple microhemorrhages, small infarcts, or both. Vascular diseases affecting the small blood vessels include hypertensive cerebrovascular disease and cerebral amyloid angiopathy. Less common entities include hereditary disorders (i.e., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and vasculitides).

Tumors of the Central Nervous System

This chapter presents the most up-to-date classification of tumors of the nervous system, based on the histological appearance of the neoplasm and on information derived from cytogenetics and molecular biology, which are now recognized worldwide as increasingly important for more precise diagnosis, prognosis, and therapeutic guidance. The chapter provides a detailed morphological description of each major tumor type, with numerous illustrations of macroscopic and microscopic lesions. First considered are primary tumors of the nervous system, including those derived from neuroepithelial tissue (astrocytic, oligodendroglial, ependymal, neuronal, and glioneuronal); pineal tissue; peripheral nerve sheath; and meninges. Next, lymphomas, hematopoietic neoplasms, and secondary (metastatic) neoplasms are described.

Acquired Diseases of the Nervous System

This chapter describes and illustrates the different neuropathological changes observed in a wide range of systemic acquired metabolic diseases that affect the central or peripheral nervous systems: hypoxia, hypoglycemia, hyperthermia, disorders of serum electrolytes, vitamin deficiencies, and exogenous intoxications, particularly alcoholism and intoxications by drugs, methanol, and heavy metals. In the central nervous system, lesions may find expression via selective involvement of some brain regions, with simultaneous complete preservation of others. The pathogenesis of the predisposition to injury for a particular anatomic region or for some specific set of cell types (neurons mostly) varies considerably form one disease to another and is undoubtedly multifactorial. The chapter also considers central nervous system abnormalities secondary to systemic diseases, including respiratory encephalopathies, hepatic encephalopathy, multifocal necrotizing leukoencephalopathy, and paraneoplastic encephalomyelopathies.

Pathology of Peripheral Nerves

This chapter describes and illustrates the pathology of peripheral nerve as it may be evaluated on nerve biopsy. After a description of the indications for the biopsy, of the special techniques commonly used, and of the normal anatomy of peripheral nerve, the general reactions of peripheral nerve to injury (primary axonal degeneration and primary segmental demyelination) are described. Neuropathies can be separated into acquired and hereditary neuropathies. Inflammatory neuropathies include immunopathologic disorders of unknown cause (inflammatory demyelinating polyradiculoneuropathy) and neuropathies due to infectious agents (leprosy) or associated with systemic vasculitis. Several neuropathies occur in association with hematologic diseases and neoplasms. Metabolic (diabetic) and toxic neuropathies are frequent. Recent advances in molecular genetics have greatly enhanced the understanding of hereditary neuropathies. These include hereditary motor and sensory neuropathies, hereditary sensory and autonomic neuropathies, and familial amyloid polyneuropathies.

Pathology of Skeletal Muscle

This chapter describes and illustrates the pathology of skeletal muscle as evaluated on muscle biopsy. After an introduction to processing techiques and the normal appearance of skeletal muscle, the basic pathologic reactions in muscle disease are described. The different categories of muscular disorders are subsequently considered and their specific morphological and eventually genetic features underlined. Involvement of the muscle secondary to denervation (neurogenic atrophies) or to neuromuscular transmission defects are first presented, followed by an account of the primary myopathies. Genetically determined diseases of skeletal muscle include muscular dystrophies, congenital myopathies, myofibrillar myopathies, and metabolic myopathies. Inflammatory myopathies may be divided into two groups, depending on whether the causative agent is a known microorganism or if the inflammatory process is believed to be an autoimmune phenomenon.

Pathology of Degenerative Diseases of the Nervous System

Degenerative diseases of the nervous system are characterized by lesions involving specific systems of functionally related neurons. The abnormality is manifest by neuronal loss with variable astrocytic and microglial reactive changes. Accumulation of specific protein aggregates (e.g., Aβ‎, tau, α‎-synuclein, TAR-DNA binding protein 43, polyglutamine) is a common feature giving rise to distinctive intracellular inclusions or extracellular deposits. For some diseases, there are well-characterized genetic abnormalities. This chapter describes and illustrates the morphological changes and genetic data in the different diseases. These are classified, per the dominant clinical features, into five categories: degenerations of the cerebral cortex (dementia), movement disorders, cerebellar ataxia, motor neuron disease, and conditions associated with autonomic failure.

Infections of the Central Nervous System

This chapter describes and illustrates the different lesions observed in central nervous system (CNS) infections. A wide variety of pathogenic infectious organisms may affect the CNS. They can be classified as pathogenic (causing diseases in every individual) or opportunistic (only affecting patients with impaired immune defenses). Bacteria may cause pyogenic infections or so-called specific infections in which the morphology of the lesions suggest a specific agent. Mycoses and parasitic infections were relatively uncommon and restricted to certain countries; however, due many factors in the modern world, including, for example, immunodeficiency of various causes and intercontinental travel, they are now more frequently encountered. Viral infections of the CNS cause lesions due to immunoallergic reactions or specific encephalitides. In AIDS, infection by HIV causes a unique encephalitis and immunodeficiency with a wide range of secondary opportunistic infections.